Occurrence and clinical management of urethral obstruction in male cats under primary veterinary care in the United Kingdom in 2016

Abstract Background Urethral obstruction (UO) has a negative effect on welfare of cats. Objectives This study aimed to determine incidence, case management, and outcomes of UO in cats in primary‐care practice in the United Kingdom. Animals All male cats under veterinary care within the VetCompass database in 2016. Methods A retrospective cohort study was performed. The electronic records of all male cats with a clinical note during the study period were searched for UO cases and were manually reviewed for inclusion. Additional demographic and clinical information were extracted on cases. Results From the study cohort of 237 825 male cats, there were 1293 incident cases. The estimated UO incidence risk during 2016 was 0.54 (95% CI: 0.51‐0.57). Demographic and clinical data were available for 1108 cases. Antibiotics were administered to 641/1108 (57.9%) cases. Overall repeat catheterization rate was 253/854 (29.6%). Repeat catheterization at 48 hours was less frequent in patients with indwelling catheters (10.1%) vs those that had a catheter placed and then immediately removed (14.8%; P = .04). Death during a UO episode was 329/1108 (29.6%), and 285/329 (88.0%) deaths involved euthanasia. Conclusions and Clinical Importance Antibiotics were commonly prescribed in cats for treatment of UO despite minimal evidence in the clinical records of bacterial cystitis. Repeat catheterization was common and case fatality rate during a UO episode was high. Repeat catheterization within 48 hours of elective removal of a urethral catheter was less common in cats that had previously had indwelling catheters. The majority of cats requiring repeat catheterization survived until the end of the study.


| INTRODUCTION
Urethral obstruction (UO) is a common emergency presentation in male cats. 1 A large retrospective study conducted on male and female cats presenting to veterinary teaching hospitals in the United States and Canada reported an overall incidence of UO of 1.5% over a 19 year period. 2 The frequency of UO in the wider primary-care population remains unknown.
UO is reported to predominantly affect young to middle aged (<7 years old) cats which are almost all males because their longer and narrower urethra (compared to females) is more likely to lead to UO. 3 Causes of UO include urethral plugs consisting of a crystalline matrix, and uroliths, although feline interstitial cystitis is reported in up to 53% of UO cases. 4 Affected cats present with a nonexpressible bladder and varying levels of cardiovascular stability and azotemia, with particular concern over hyperkalemia-induced bradyarrhythmia. 5 Approaches to UO case management discussed in the literature are varied and include both inpatient and outpatient treatment, with limited standardization of treatment options. For example, there are varied reported durations recommended for indwelling catheters, and the use of additional pharmacological aids such as urethral muscle relaxants are controversial. 1 There is a high risk of UO recurrence (rUO), reported at 11% to 40% of cases 4,6-8 ; however, comparison between studies is difficult because of variation in treatment methods and patient follow-up period. Several studies have investigated factors associated with reduced rUO including size and duration of indwelling urethral catheters, use of antibiotics, and additional treatments such as urethral relaxants and antispasmodics. 1,[6][7][8][9] However, factors associated with rUO have not been consistent between studies. For example, 1 study suggested reduced rUO rates with longer catheterization duration, 6 and another found no difference. 7 Most published literature on UO in cats is based on information from referral centers, rather than primary-care practices. This study aimed to estimate incidence of UO diagnosed in cats attending primary-care practices in the United Kingdom participating in VetCompass, to document the current standards of care applied in these practices and to evaluate survival and recurrence after diagnosis of UO. Finally, we hypothesized that presence of an indwelling urethral catheter is associated with a reduced recurrence rate.

| MATERIALS AND METHODS
A retrospective cohort study was conducted with a sampling frame of all male cats under veterinary care within the VetCompass database for a 1-year period from January 1, 2016 to December 31, 2016. VetCompass collects and collates anonymized electronic patient records (EPR) from enrolled primary-care veterinary practices in the United Kingdom. 10  charity practice, referral practice) and survival. Please note that throughout the manuscript, the term catheterization will refer to urethral catheterization. The urethral catheter composition was determined following data collection to provide a standard set of materials, and to avoid use of brand names. General anesthesia was defined as receiving inhalant anesthetics or notation of "general anesthesia" in the EPR, all other patients receiving pharmacological restraint were classified as sedated. EPRs were checked until their final available record at the time of data collection in April 2020 to June 2020 for evidence of repeat catheterization or mortality. A deobstruction attempt was defined as any attempt at relieving UO and included manual bladder expression and catheterization attempts. A catheterization attempt was defined as any recorded attempt at urethral catheter placement to manage a UO episode and because of inconsistent recording may include multiple catheters, or multiple insertions of the same catheter. Successful catheterization was defined as a recorded catheterization attempt that resulted in voiding of urine and decompression of the bladder. Additional attempts were defined as catheterization attempted under a separate sedation or anesthetic. Death related to UO was defined as evidence of mortality during a UO episode and was further categorized as euthanasia, unassisted or unrecorded.
Data were checked and cleaned in a spreadsheet (Microsoft Office Excel 2016). Cases with evidence of presentation at another practice before the presentation at the current practice for the same UO event were excluded from incidence calculations to prevent possible double counting of records and to allow for greater completeness of data relating to initial assessment and treatment. Cases with evidence of transfer to another practice after initial diagnosis were removed from subsequent analysis of diagnostic and therapeutic management of UO. Incidence described an annual incidence risk and was calculated as the proportion of all male cats under primary veterinary care in 2016 that were diagnosed with UO in the study period. The confidence interval estimates for incidence risk were derived from standard errors, based on approximation to the binomial distribution. 12 Descriptive statistics were generated for UO cases. Continuous variables were summarized using median, interquartile range (IQR) and range.
Ethical approval for this study was obtained from the Ethics and Welfare Committee at the author's institution for this study (unique reference number: SR2018-1652).

| Statistical analysis
A commercial statistical software program was used for all analyses (SPSS Statistics, version 26; IBM). Binary categorical variables were compared using chi-square tests. Significance was set at P < .05.  Electronic patient records documented that cases were transferred to a charity practice in 90/1293 (7.0%) cases, another general practice in 89/1293 (6.9%) cases or referral practice in 6/1293 (0.5%) cases. Cases that were transferred to another practice were not included in further analysis of diagnostics, treatment, and outcome because of a lack of follow up information, leaving 1108 cases for reporting of clinical management.

| Therapeutics
A summary of therapeutics administered is found in

| Outcome
Outcome and recurrence data are summarized in Figure 1 and Table 3.
Repeat catheterization was most common within 48 hours after catheter catheter being placed and then immediately removed, and found an odds ratio of 3 : 1 for increased risk of recurrence of UO in the outpatient group. 8 These findings, in conjunction with our data, support the use of indwelling catheters to reduce rUO rates. However, repeat catheterization rates for cases in our study with in-out catheterization were lower than previously reported, 8  While a retrospective study found that 44% of cats with UO had positive urine bacterial culture, urine was obtained from the indwelling urethral catheter in several cases and also from cats with recent previous catheterization. 17  devices. 19 Instead, cystocentesis and urine culture of cats that develop persistent cystitis signs after removal of a urethral catheter is recommended. 19 Analgesia was administered to 85% of cases as part of the treatment of UO. Urethral obstruction is thought to be a painful condition Cats with UO can present along a spectrum of hemodynamic instability because of potential for life-threatening hyperkalemia. 5 Calcium gluconate, insulin, and sodium bicarbonate were used infrequently in cats in this study, with only 3%, 1%, and 0.3% receiving them, respectively. In the current EPR format, we are unable to say whether this represents a lack of requirement for these therapies because cats were less severely affected, whether they were given but not recorded, or whether primary care practices were not evaluating these cases for the presence of hyperkalemia.
An variety of therapeutics aimed to cause urethral relaxation or reduce urinary tract inflammation were administered to the UO cases in the current study. Currently, there is little evidence for or against the use of any of the medications described for feline UO management. The most commonly administered drug in this study was prazosin, an α1-adrenergic antagonist which causes smooth muscle relaxation. The proximal third of the feline urethra is comprised of smooth muscle with the remaining distal tissue comprising of skeletal muscle 26 where α-1-adrenergic antagonists will have no effect. The majority of obstructions are thought to occur in the distal urethra 27 and despite the frequent use of prazosin in cats with UO, there is little evidence to suggest any benefit. Although a retrospective study showed reduced risk of rUO in cats treated with prazosin compared to cats receiving phenoxybenzamine, 7 a recent double-blinded, prospective, interventional study did not identify a difference in the rate of rUO in cats receiving prazosin, although this study was underpowered to detect a difference. 9 Hypotension is an adverse effect of prazosin, so it isrecommended to monitor blood pressure during treatment. 9 L-Tryptophan containing supplements were frequently prescribed in this study. Tryptophan is an essential amino acid and precursor to both melatonin and serotonin which has been implicated in the susceptibility of cats to stress. 28 In a recent study there was a reduced rate of rUO of LUTD signs in cats receiving a therapeutic urinary stress diet; however, none of these cats had UO. 29 It is thought that stress could contribute to the pathophysiology of FLUTD and development of an inflammatory cystitis; however, only 1 study has found a direct association between stress and urinary bladder changes. 30 Interestingly, diazepam was administered orally in 94/1108 (8.5%) cases. Diazepam (PO) is associated with idiosyncratic acute hepatic necrosis in cats 31,32 and has no effect on distal urethral pressures in experimental studies when administered IV, 33  Long term rUO has been assessed in 2 previous studies with rates of 24% and 36% for 2 and 3 years, respectively. 4,34 As patient records were monitored to the time of data collection, our study period covered more than a 3-year period for many cats, suggesting our rUO rate was similar to previous literature.
Our study identified that 29.6% of the cases did not survive the initial UO event. Urethral obstruction has previously been reported with a case fatality rate of 6.4% to 26.0%. 4,5,17 The variation in reported case fatalityrate is likely impacted by the heterogeneity of follow-up duration and the type of clinic to which the cat presents to (referral vs primary-care). As seen in Figure 1 There were several limitations in this study. The EPR data were not originally recorded for research purposes, so information may have been inconsistently recorded. This prevented more detailed evaluation of parameters, for example duration of indwelling catheters before removal or size of catheter, or for assessment of electrocardiogram abnormalities and presence of hyperkalemia. As such, it is not possible to conclude whether absence of recorded details could be safely taken to confirm true absence. One example is the low levels of recording of chronic management strategies such as multimodal environmental modification (MEMO). MEMO has been associated with reduced recurrence of nonobstructive FLUTD 24 ; however, we were unable to assess its implementation in our study because of inconsistent EPR documentation. Similarly, biochemistry, urinalysis and culture results were infrequently documented, limiting their inclusion. EPRs were evaluated until the last recorded entry; however, cats that moved to another veterinary practice after their UO may have been lost to follow up and therefore the true longer-term rUO and case fatality rates maight be underestimated. Insurance and financial data were not available for this study. Demographic data such as neuter status was not manually checked in the EPR which could explain our large number of entire animals. It is possible that our high case fatality rate was influenced by financial constraints, or by recommendations based on previous literature of high rUO rates. Because of the higher case fatality rate demonstrated in this study, it is possible that repeat catheterization rates were artificially lowered by patients being euthanized.